Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations

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dc.contributor.authorvan de Wouw, Marcel
dc.contributor.authorBoehme, Marcus
dc.contributor.authorLyte, Joshua M.
dc.contributor.authorWiley, Niamh
dc.contributor.authorStrain, Conall R.
dc.contributor.authorO'Sullivan, Orla
dc.contributor.authorClarke, Gerard
dc.contributor.authorStanton, Catherine
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2020-02-18T16:35:35Z
dc.date.available2020-02-18T16:35:35Z
dc.date.issued2018-07-01
dc.date.updated2020-02-18T16:23:55Z
dc.description.abstractThere is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota‐derived metabolites play a central role in the communication between microbes and their host, with short‐chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress‐induced alterations in reward‐seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test‐specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress‐induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota‐targeted therapies for stress‐related disorders.en
dc.description.sponsorshipScience Foundation Ireland (SFI (15/JP-HDHL/3270; JPI-HDHL-NutriCog project ‘AMBROSIAC)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationvan de Wouw, M., Boehme, M., Lyte, J. M., Wiley, N., Strain, C., O'Sullivan, O., Clarke, G., Stanton, C., Dinan, T. G. and Cryan, J. F. (2018) 'Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations', The Journal of Physiology, 596(20), pp. 4923-4944. doi: 10.1113/jp276431en
dc.identifier.doi10.1113/jp276431en
dc.identifier.endpage4944en
dc.identifier.issn0022-3751
dc.identifier.issued20en
dc.identifier.journaltitleJournal of Physiologyen
dc.identifier.startpage4923en
dc.identifier.urihttps://hdl.handle.net/10468/9664
dc.identifier.volume596en
dc.language.isoenen
dc.publisherWileyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.urihttps://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP276431
dc.rights© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society; This is the peer reviewed version of the following article: (2018), Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations. J Physiol, 596: 4923-4944, which has been published in final form at https://doi.org/10.1113/JP276431 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en
dc.subjectGut microbiotaen
dc.subjectBehaviouren
dc.subjectChronic stressen
dc.titleShort-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterationsen
dc.typeArticle (peer-reviewed)en
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